Identification

Summary

Polythiazide is a thiazide diuretic used in the management of hypertension and treatment of edema.

Brand Names
Minizide, Renese, Renese-R
Generic Name
Polythiazide
DrugBank Accession Number
DB01324
Background

A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p826)

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 439.882
Monoisotopic: 438.970880311
Chemical Formula
C11H13ClF3N3O4S3
Synonyms
  • Polythiazide

Pharmacology

Indication

Polythiazide is a thiazide diuretic used to decrease edema and decrease blood pressure.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

As a thiazide diuretic, Polythiazide inhibits the sodium-chloride symporter which decreases solute reabsorption leading to a retention of water in the urine, as water normally follows solutes. More frequent urination is due to the increased loss of water that has not been retained from the body as a result of a concomitant relationship with sodium loss from the convoluted tubule. The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure

Mechanism of action

As a diuretic, polythiazide inhibits active chloride reabsorption at the early distal tubule via the thiazide-sensitive Na-Cl cotransporter (TSC), resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like polythiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of polythiazide may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.

TargetActionsOrganism
ASolute carrier family 12 member 3
inhibitor
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

Not Available

Pathways
PathwayCategory
Polythiazide Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirPolythiazide may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy.
AbciximabThe therapeutic efficacy of Abciximab can be decreased when used in combination with Polythiazide.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Polythiazide.
AcebutololThe therapeutic efficacy of Acebutolol can be increased when used in combination with Polythiazide.
AceclofenacThe therapeutic efficacy of Polythiazide can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Polythiazide can be decreased when used in combination with Acemetacin.
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be decreased when used in combination with Polythiazide.
AcetaminophenPolythiazide may increase the excretion rate of Acetaminophen which could result in a lower serum level and potentially a reduction in efficacy.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Polythiazide.
AcetyldigitoxinPolythiazide may increase the hypokalemic activities of Acetyldigitoxin.
Interactions
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Food Interactions
  • Avoid alcohol. Alcohol may potentiate orthostatic hypotension.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ReneseTablet4 mg/1OralPfizer Labs2005-12-14Not applicableUS flag
ReneseTablet2 mg/1OralPfizer Labs2005-12-14Not applicableUS flag
ReneseTablet1 mg/1OralPfizer Labs2005-12-14Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
MinizidePolythiazide (0.5 mg/1) + Prazosin hydrochloride (2 mg/1)CapsuleOralPfizer Labs2006-10-05Not applicableUS flag
MinizidePolythiazide (0.5 mg/1) + Prazosin hydrochloride (1 mg/1)CapsuleOralPfizer Labs2006-10-05Not applicableUS flag
MinizidePolythiazide (0.5 mg/1) + Prazosin hydrochloride (5 mg/1)CapsuleOralPfizer Labs2006-10-05Not applicableUS flag
Renese-RPolythiazide (2 mg/1) + Reserpine (25 mg/1)TabletOralUNSPECIFIED2006-02-06Not applicableUS flag

Categories

ATC Codes
C03AA05 — PolythiazideG01AE10 — Combinations of sulfonamidesC03AB05 — Polythiazide and potassium
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as 1,2,4-benzothiadiazine-1,1-dioxides. These are aromatic heterocyclic compounds containing a 1,2,4-benzothiadiazine ring system with two S=O bonds at the 1-position.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Thiadiazines
Sub Class
Benzothiadiazines
Direct Parent
1,2,4-benzothiadiazine-1,1-dioxides
Alternative Parents
Secondary alkylarylamines / Organosulfonamides / Benzenoids / Aryl chlorides / Aminosulfonyl compounds / Sulfenyl compounds / Dialkylthioethers / Azacyclic compounds / Organopnictogen compounds / Organofluorides
show 4 more
Substituents
1,2,4-benzothiadiazine-1,1-dioxide / Alkyl fluoride / Alkyl halide / Amine / Aminosulfonyl compound / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzothiadiazine (CHEBI:8327)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
36780APV5N
CAS number
346-18-9
InChI Key
CYLWJCABXYDINA-UHFFFAOYSA-N
InChI
InChI=1S/C11H13ClF3N3O4S3/c1-18-10(4-23-5-11(13,14)15)17-7-2-6(12)8(24(16,19)20)3-9(7)25(18,21)22/h2-3,10,17H,4-5H2,1H3,(H2,16,19,20)
IUPAC Name
6-chloro-2-methyl-1,1-dioxo-3-{[(2,2,2-trifluoroethyl)sulfanyl]methyl}-3,4-dihydro-2H-1λ⁶,2,4-benzothiadiazine-7-sulfonamide
SMILES
CN1C(CSCC(F)(F)F)NC2=CC(Cl)=C(C=C2S1(=O)=O)S(N)(=O)=O

References

General References
Not Available
Human Metabolome Database
HMDB0015419
KEGG Drug
D00657
KEGG Compound
C07766
PubChem Compound
4870
PubChem Substance
46508633
ChemSpider
4704
RxNav
8565
ChEBI
8327
ChEMBL
CHEMBL1587
Therapeutic Targets Database
DAP000751
PharmGKB
PA164748763
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Polythiazide

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Pfizer Inc.
Dosage Forms
FormRouteStrength
CapsuleOral
TabletOral1 mg/1
TabletOral2 mg/1
TabletOral4 mg/1
TabletOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)214 °CPhysProp
logP1.90SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.264 mg/mLALOGPS
logP2.13ALOGPS
logP1.1ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)9.31ChemAxon
pKa (Strongest Basic)-3.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area109.57 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity90.52 m3·mol-1ChemAxon
Polarizability37.56 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9884
Blood Brain Barrier-0.5727
Caco-2 permeable-0.6601
P-glycoprotein substrateSubstrate0.6985
P-glycoprotein inhibitor INon-inhibitor0.7714
P-glycoprotein inhibitor IINon-inhibitor0.8974
Renal organic cation transporterNon-inhibitor0.776
CYP450 2C9 substrateNon-substrate0.6019
CYP450 2D6 substrateNon-substrate0.8108
CYP450 3A4 substrateNon-substrate0.5091
CYP450 1A2 substrateNon-inhibitor0.7786
CYP450 2C9 inhibitorNon-inhibitor0.5713
CYP450 2D6 inhibitorNon-inhibitor0.8479
CYP450 2C19 inhibitorNon-inhibitor0.7738
CYP450 3A4 inhibitorInhibitor0.6198
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6625
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.8224
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.3534 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8884
hERG inhibition (predictor II)Non-inhibitor0.8734
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Key mediator of sodium and chloride reabsorption in this nephron segment, accounting for a significant fraction of renal sodium reabsorption.
Gene Name
SLC12A3
Uniprot ID
P55017
Uniprot Name
Solute carrier family 12 member 3
Molecular Weight
113138.04 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  2. Monroy A, Plata C, Hebert SC, Gamba G: Characterization of the thiazide-sensitive Na(+)-Cl(-) cotransporter: a new model for ions and diuretics interaction. Am J Physiol Renal Physiol. 2000 Jul;279(1):F161-9. [Article]
  3. Frindt G, McNair T, Dahlmann A, Jacobs-Palmer E, Palmer LG: Epithelial Na channels and short-term renal response to salt deprivation. Am J Physiol Renal Physiol. 2002 Oct;283(4):F717-26. [Article]
  4. Gamba G: The thiazide-sensitive Na+-Cl- cotransporter: molecular biology, functional properties, and regulation by WNKs. Am J Physiol Renal Physiol. 2009 Oct;297(4):F838-48. doi: 10.1152/ajprenal.00159.2009. Epub 2009 May 27. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Duarte JD, Cooper-DeHoff RM: Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide-like diuretics. Expert Rev Cardiovasc Ther. 2010 Jun;8(6):793-802. doi: 10.1586/erc.10.27. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Vallon V, Rieg T, Ahn SY, Wu W, Eraly SA, Nigam SK: Overlapping in vitro and in vivo specificities of the organic anion transporters OAT1 and OAT3 for loop and thiazide diuretics. Am J Physiol Renal Physiol. 2008 Apr;294(4):F867-73. doi: 10.1152/ajprenal.00528.2007. Epub 2008 Jan 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Vallon V, Rieg T, Ahn SY, Wu W, Eraly SA, Nigam SK: Overlapping in vitro and in vivo specificities of the organic anion transporters OAT1 and OAT3 for loop and thiazide diuretics. Am J Physiol Renal Physiol. 2008 Apr;294(4):F867-73. doi: 10.1152/ajprenal.00528.2007. Epub 2008 Jan 23. [Article]

Drug created at June 30, 2007 17:21 / Updated at February 21, 2021 18:51